DESCRIPTION: (Verbatim from the Applicant's Abstract) The hypothesis underlying this proposal is that cannabinoids are endogenous neuroprotectants in cerebral ischemia. This hypothesis is based on several distinct observations, which include the fact that physiological events that occur during cerebral ischemia would be expected to enhance the synthesis and release of endogenous cannabinoids. Exogenously administered synthetic cannabinoid analogs can protect neuronal cultures from ischemia-like conditions, can reduce hippocampal neuronal loss after transient global ischemia, and can reduce infarct volume after permanent MCA occlusion in rat brain. Furthermore these neuroprotective actions of cannabinoids are in keeping with their ability to reduce voltage-gated calcium currents, enhance inwardly rectifying potassium currents, and inhibit glutamate release.